Bradley E. Alger Ph.D.

Personal History:

I completed undergraduate work at the University of California, Berkeley in 1972, and obtained my Ph.D. from Harvard University in 1977. My thesis was on extracellular electrophysiology in the rat hippocampal slice and included some of the early studies on LTP. My postdoctoral training was with Roger Nicoll at UCSF. In 1981, I became an Assistant Professor in Department of Physiology at UMAB and in 1992 was promoted to Professor with tenure. In 2014, I was promoted to Professor Emeritus.

Research Interests:

My colleagues and I studied the neurophysiological basis of epilepsy and of learning and memory in the mammalian brain. These disparate phenomena have common features: They have prominent electrophysiological manifestations in the hippocampus, they can be modeled in an in vitro brain slice preparation, and their occurrence depends on the state of neuronal excitability in the tissue. We used state-of-the-art electrophysiological techniques (intracellular, whole-cell, patch-clamp, field potential) in the hippocampal slice to investigate an aspect of excitability control that is crucial for the establishment of memory traces and for the prevention of epileptic seizures: the strength of synaptic inhibition mediated by the neurotransmitter, GABA. Decreases in GABA inhibition facilitate the induction of long-term potentiation (LTP), an increase in synaptic excitation that is the primary candidate for the neurophysiological basis of learning and memory.

Decreases in GABA inhibition also promote the onset of the epileptic seizure, a state of hyperexcitability characteristic of epilepsy. How does the nervous system maintain the fine distinction necessary to encourage the former while preventing the latter? What cellular controls on inhibition are normally present in the brain and how are these controls altered in physiological and pathophysiological ways? These are the sorts of questions we tried to answer. We discovered a new mode of cellular communication that may solve part of the puzzle: the target (pyramidal) cells, the ones towards which inhibition is directed, may regulate their own state of inhibition by sending a signal backwards across the synaptic junctions (retrograde signaling) and thereby causing the inhibitory interneurons to stop releasing GABA temporarily.

Many laboratories have begun studying this phenomenon, and the most interesting and surprising thing is that the signal from the pyramidal cell to the interneuron is a molecule that has been called "the brain's own marijuana". In the mammalian brain are specialized receptors that recognize and bind to the active ingredient in marijuana, THC. The natural compound that is active at these receptors is not THC, of course, but an "endocannabinoid", a molecule recently recognized as capable of carrying signals between brain cells. How do these molecules normally work? What can they teach us about the mechanisms of drug abuse and potential medical use of marijuana and other cannabinoids?